Double-Bond Isomerization: Highly Reactive Nickel Catalyst Applied in the Synthesis of the Pheromone (9 Z,12 Z)-Tetradeca-9,12-dienyl Acetate

Article abstract of DOI:10.1021/acs.orglett.5b01230

A highly reactive nickel catalyst comprising NiCl₂(dppp) or NiCl₂(dppe) with zinc powder, ZnI₂ and Ph₂PH, was applied in the isomerization of terminal alkenes to Z-2-alkenes. The double-bond geometry of the 2-alkene can be controlled via the reaction temperature to yield the 2-Z-alkenes in excellent yields and high Z-selectivities. The formation of other constitutional isomers, such as 3-alkenes, is suppressed on the basis of the proposed mechanism via a 1,2-hydride shift from the metal to the Ph₂P ligand. The nickel-catalyzed isomerization reaction was then applied in the synthesis of (9Z,12Z)-tetradeca-9,12-dienyl acetate, a pheromone with a 2Z,5Z-diene subunit.

Full text of DOI:10.1021/acs.orglett.5b01230

Letter
pubs.acs.org/OrgLett
Double-Bond Isomerization: Highly Reactive Nickel Catalyst Applied
in the Synthesis of the Pheromone (9Z,12Z)‑Tetradeca-9,12-dienyl
Acetate
Felicia Weber, Anastasia Schmidt, Philipp Rose, Michel Fischer, Olaf Burghaus, and Gerhard Hilt*
̈
Fachbereich Chemie, Philipps-Universitat Marburg, Hans-Meerwein-Straße 4, D-35043 Marburg, Germany
̈
S
* Supporting Information
ABSTRACT: A highly reactive nickel catalyst comprising
NiCl2(dppp) or NiCl2(dppe) with zinc powder, ZnI2 and
Ph2PH, was applied in the isomerization of terminal alkenes to
Z-2-alkenes. The double-bond geometry of the 2-alkene can be
controlled via the reaction temperature to yield the 2-Z-alkenes
in excellent yields and high Z-selectivities. The formation of
other constitutional isomers, such as 3-alkenes, is suppressed on the basis of the proposed mechanism via a 1,2-hydride shift from
the metal to the Ph2P ligand. The nickel-catalyzed isomerization reaction was then applied in the synthesis of (9Z,12Z)-tetradeca-
9,12-dienyl acetate, a pheromone with a 2Z,5Z-diene subunit.
Scheme 1. Cobalt-Catalyzed Isomerization of Terminal
Alkenes
he selective isomerization of terminal alkenes into 2-
Talkenes has been investigated for decades utilizing
different transition-metal catalysts.1 A general feature of these
catalysts is the proposed reaction mechanism in which the
formation of the reactive transition-metal hydride species is
postulated. These metal hydride species undergo reversible
addition/elimination to the alkene, which leads to a change in
the double-bond position within the molecule.2 This explains
that, in many transformations, the formation of the other
constitutional isomers of the alkene is not easily suppressed
when isomerization along an unsubstituted carbon chain is
possible. The isomerization of a terminal alkene into a 2-alkene,
with high ratios of the Z-configured double bond, is only
successfully observed if two conditions are fulfilled: (a) the
terminal alkene starting material has a higher binding affinity
than the 2-alkene as well as the other constitutional isomers
and (b) the Z-isomer is predominantly formed in a kinetically
controlled process.3,4 In both cases, the ligand system plays an
important role in these reactions. The coordination sphere
around the transition metal must not only restrict the
coordination of the 1-alkene, but also repulsive steric
interactions between the substituents of the alkene and the
ligand system must be strong enough for the selective β-hydride
elimination of the pro-Z hydrogen from the intermediately
formed alkyl−metal complex.
The cobalt precatalyst CoBr2(dppp) is easy to handle. In the
presence of reducing agent (Zn), the mild Lewis acid ZnI2, and
the coligand Ph2PH, the reactions proceeded in a rather short
period of time at ambient temperatures. While for a number of
alkenes very good results could be obtained, the catalyst system
exhibits two drawbacks: First, for an increase in Z-selectivity,
lowering the reaction temperature should be advantageous to
favor the kinetic product, but with the cobalt catalyst
significantly reduced reactivity was observed. Second, increasing
the reactivity by heating the dichloromethane solution did not
result in better conversions of sterically hindered starting
materials when the cobalt catalyst system was utilized.
Therefore, the temperature corridor for the cobalt-catalyzed
process is narrow, and this will be problematic, particularly
when branched alkenes and functionalized alkenes are used.4
Accordingly, we investigated the reactivity of neighboring
nickel catalysts, namely NiBr2(dppp), in an isomerization
reaction.1g,5,6 To our delight, the isomerization of 1-octene with
the cobalt catalyst system, which took 1 h at ambient
temperatures for the formation of the desired 2-Z-alkene, was
completed with the NiBr2(dppp), Zn, ZnI2, Ph2, and PH
catalyst mixture within a few minutes at room temperature.
This considerable increase in reactivity by orders of magnitude
Some time ago, we identified a cobalt−catalyst system which
led to significantly better results compared to many other
transition-metal catalysts for the isomerization of terminal
alkenes toward Z-2-alkenes. In these reactions, PPh2H was used
as coligand, which made the significant impact (Scheme 1).4
The cobalt catalyst allows not only formation of the desired
2-Z-alkenes but also suppression of the formation of higher
alkenes.
Received: April 27, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b01230
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
intrigued us to investigate the nickel-catalyzed reaction in more
detail. Most importantly, the isomerization reaction could be
performed at lower temperatures, and eventually, the isomer-
ization of 1-alkene to the 2-Z-alkene was still successful at
temperatures as low as −50 °C and went to completion within
only 2 h reaction time, resulting in the formation of the 2-Z-
alkene in an excellent E/Z ratio of 1:30. This outstanding result
led us to the conclusion that a highly reactive nickel catalyst
could be useful for the isomerization of terminal alkenes when
the reaction temperature is adjusted to find the right balance
between reactivity and selectivity. Accordingly, the isomer-
ization reactions of various terminal alkenes were investigated
using the nickel precatalyst NiBr2(dppp) with Ph2PH as co-
ligand under the conditions exemplified in Scheme 2.
Table 1. Results of the Nickel-Catalyzed Isomerization of
Terminal Alkenes
a
Scheme 2. Nickel-Catalyzed Isomerization of Terminal
Alkenes
The results of these transformations are summarized in Table
1. The application of unbranched alkenes (3a/3b) led to the
desired 2-Z-alkenes with good results. The nickel catalyst
system is by far more reactive for unbranched terminal aliphatic
alkenes than the cobalt catalyst system. Even at temperatures as
low as −60 °C, the nickel catalyst is able to catalyze the
isomerization, whereas the cobalt catalyst is essentially
unreactive for most starting materials below room temperature.
Unfortunately, longer alkyl side chains, such as in 1-hexadecene,
are at a disadvantage since these starting materials solidify at
−60 °C and are not converted at these temperatures. At
elevated temperatures (room temperature), the isomerization is
complete within minutes, but the E/Z ratio is only moderate.
Nevertheless, branched alkenes, such as 3c−e, could be applied
successfully at somewhat elevated temperatures (−15 to −40
°C) (Table 1, entries 3−5). Although 4c was accompanied by
larger amounts of the other constitutional isomers (8%), this
represents a considerable improvement compared to the cobalt-
catalyst system, where branched alkenes could not be applied
successfully. Also, functional groups, such as a silyl-function-
alized alkene, as well as a number of silyl-protected oxygen-
functionalized alkenes 3f−j were applicable with good to
excellent results. Of particular interest was the substrate 3j
where only the chemoselective isomerization of the allyl ether
functionality was observed, while the other terminal double
bond remained untouched. This result can be rationalized in
that the nickel catalyst does not coordinate well to silyl-
protected oxygen donors for steric reasons but has a
pronounced tendency to coordinate to the much less hindered
ether donor functionality. When the reaction of 3j was
continued for more than 4 h at −30 °C, isomerization of the
other double bond accompanied by other isomers was
observed. In addition, the isomerization of the allyl phenyl
ether led to the 2-E-alkene 4i when the cobalt-catalyst system
was applied. In contrast, the nickel catalyst produced the Z-
isomer in good yield and very good Z-selectivity (E/Z = 5:95).
Finally, we investigated the application of pinacol boronic
esters 3k−n in the nickel-catalyzed isomerization reaction. The
double-bond migration alters the reactivity of the boron-
a
Reaction conditions: NiBr2(dppp) (10 mol %), Zn, ZnI2 (20 mol %
each), Ph2PH (5 mol %), 1-alkene 3 (0.5 mmol, 1.0 equiv), CH2Cl2;
different reaction temperatures and times are listed in the table. The
reaction temperature was adjusted with a dry ice/acetone bath.
Unreacted starting material and other isomers were not separated and
are included in the yield. Conversion and E/Z ratio were determined
by 1H NMR spectroscopy and GC or GC−MS analysis (Pin =
pinacol).
functionalized building blocks so that allylboron products were
obtained at low temperatures.7
The isomerization of these boron-functionalized starting
materials, such as 3l, leads to 4l in a good yield of 80% with a
B
DOI: 10.1021/acs.orglett.5b01230
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
very good E/Z-selectivity of 3:97. In a similar fashion, the vinyl
boronic esters 4k and 4n could be of interest for cross-coupling
reactions or metatheses.8 The results concerning in situ follow-
up reactions of these materials are under investigation.
Some of the nickel-catalyzed isomerization reactions should
be stopped before the starting material is consumed completely.
Otherwise, the 2Z-configured products will be converted into
the thermodynamically more stable 2E-isomer or into the
undesired other constitutional isomers (see the Supporting
Information).
tetradeca-9,12-dienyl acetate 10, which was identified as a
pheromone component of the species Spodoptera exigua (owlet
moth), as the synthetic target.9 The challenges for a nickel-
catalyzed isomerization reaction are 3-fold: (a) the catalyst
must generate the 12Z-double bond with high Z-selectively; (b)
the isomerization must not convert the 9Z,12Z-diene subunit
into a conjugated diene (e.g., 9Z,11Z-diene); and (c) the
double-bond configuration at position 9 must not be altered by
the catalyst.
The synthesis of the pheromone precursor was initiated from
the commercially available diol 7, which was converted into the
monoprotected alcohol followed by a Swern oxidation, leading
to the aldehyde 8 in 64% yield over two steps (Scheme 4).
After a Z-selective Wittig reaction of 8 with 1-pentenyltriphe-
nylphosphorylide, deprotection, and acetylation, the 1,5-diene 9
was generated in 68% yield over three steps.
From a mechanistic point of view, we are convinced that the
reactive catalyst species is a nickel complex with dppp and
Ph2PH in the ligand sphere. The presence of an additional
bromide ligand (see the Supporting Information, EPR
measurements) is possible; EPR measurements are inconclusive
as an equilibrium between a NiIBr(dppp)(PHPh2) complex and
a cationic [NiI(dppp)(PHPh2)]+ species could explain the
hyperfine coupling pattern of the EPR spectra. Theoretical
investigations are underway to verify the proposed mechanism
in terms of ligand sphere and chemo-/stereoselectivities.
A major difference between the cobalt and nickel systems can
be observed in electroanalytical measurements. The cyclic
voltammograms of the CoBr2(dppp) complex changed
significantly after addition of zinc powder and zinc iodide,
indicating that the cobalt(II) is easily reduced by zinc powder
in the presence of a Lewis acid, such as zinc iodide, to the
corresponding cobalt(I) complex (see the Supporting In-
formation). This change in oxidation state is easily visible by a
distinct color change of the dichloromethane solution from
blue to red. In contrast, the corresponding cyclic voltammo-
grams of the nickel complex NiBr2(dppp) exhibit no significant
change after addition of zinc powder and zinc iodide. However,
after addition of Ph2PH to this mixture, the cyclic voltammo-
grams showed new peaks, in combination with the character-
istic color change from red to deep brown. In addition, the EPR
measurements indicated that under these reaction conditions a
paramagnetic nickel(I) species is formed via reduction of the
nickel(II) precursor.
Scheme 4. Synthesis of Pheromone 10 via a Nickel-
Catalyzed Isomerization in the Key Step
Originally, the NiBr2(dppp) complex was applied for the
isomerization of 9 as reported before. However, the additional
5Z-double bond had a significant influence upon this nickel-
catalyzed reaction, resulting in a very moderate 1:2 E/Z
selectivity. A short screening of bidentate phosphine ligands
revealed that for NiCl2(dppe) as catalyst precursor the best
results were obtained. Accordingly, the isomerization of 9
utilizing NiCl2(dppe)6 as catalyst precursor gave the desired
product 10 in 92% yield as a mixture of E/Z = 12:88 (96%
conversion after 8 h reaction time at −15 °C). The 9Z,12Z-
configured product could be purified on a silver nitrate doped
silica gel column to obtain 10 with significantly increased purity
(>95%).10
Accordingly, we propose the 1,2-hydride shift from the metal
(5) to the ligand (6) to be a crucial step in the reaction
mechanism, in line with the proposed mechanism of the cobalt-
catalyzed isomerization reaction. Therefore, the formation of
other constitutional isomers via metal hydride readdition to the
2-alkene followed by β-hydride elimination might be prohibited
(Scheme 3).
In order to further illustrate the usefulness of the nickel-
catalyzed isomerization reaction, we selected (9Z,12Z)-
Scheme 3. Proposed Key Step (5 → 6) in the Mechanism of
In conclusion, we were able to show that a nickel-catalyzed
isomerization of terminal alkenes to Z-2-alkenes can be realized.
As in the cobalt-catalyzed reaction, Ph2PH must be present to
initiate the reaction. The isomerization, which can be
performed at temperatures as low as −60 °C, led predom-
inantly to the Z-configured isomers, and the catalyst tolerates a
number of functional groups which will be useful in follow-up
reactions. A considerable improvement of the nickel-catalyzed
process over the cobalt-catalyzed isomerization is the possibility
of applying branched alkenes with good to excellent success. In
addition, the nickel-catalyzed isomerization of terminal alkenes
was applied in the synthesis of pheromone 10 with good
success, despite a challenging and sensitive 9Z,12Z-diene
subunit.
the Nickel-Catalyzed Isomerization Reaction
C
DOI: 10.1021/acs.orglett.5b01230
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
62, 1993. (g) Hoffmann, R. W.; Landmann, B. Chem. Ber. 1986, 119,
1039−1053.
(8) (a) Morrill, C.; Grubbs, R. H. J. Org. Chem. 2003, 68, 6031−
6034. (b) Chausset-Boissarie, L.; Ghozati, K.; LaBine, E.; Chen, J. L.-
Y.; Aggarwal, V. K.; Crudden, C. M. Chem.Eur. J. 2013, 19, 17698−
17701.
(9) Tumlinson, J. H.; Mitchell, E. R.; Yu, H.-S. J. Chem. Ecol. 1990,
16, 3411−3423.
(10) No difference in yield or selectivities was observed when either
nickel chloride or nickel bromide complexes were applied. Therefore,
we rationalize that the halides are not part of the active species.
ASSOCIATED CONTENT
* Supporting Information
Synthesis, analytical data, and NMR spectra. The Supporting
Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.orglett.5b01230.
■
S
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: hilt@chemie.uni-marburg.de. Fax: +49 6421 2825677.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the German Science Foundation (Hi655 17-1) for
financial support.
REFERENCES
■
(1) (a) Krompiec, S.; Krompiec, M.; Penczek, R.; Ignasiak, H. Coord.
Chem. Rev. 2008, 252, 1819−1841. (b) Larsen, C. R.; Erdogan, G.;
Grotjahn, D. B. J. Am. Chem. Soc. 2014, 136, 1226−1229. (c) Larsen,
C. R.; Grotjahn, D. B. J. Am. Chem. Soc. 2012, 134, 10357−10360.
(d) Zhuo, L.-G.; Yao, Z.-K.; Yu, Z.-X. Org. Lett. 2013, 15, 4634−4637.
(e) Ahlsten, N.; Bartoszewicza, A.; Martin-Matute, B. Dalton Trans.
2012, 41, 1660−1670. (f) Punner, F.; Schmidt, A.; Hilt, G. Angew.
̈
Chem., Int. Ed. 2012, 51, 1270−1273. (g) Lim, H. J.; Smith, C. R.;
Rajanbabu, T. V. J. Org. Chem. 2009, 74, 4565−4572. (h) Mamone, P.;
Grunberg, M. F.; Fromm, A.; Khan, B. A.; Gooßen, L. J. Org. Lett.
̈
2012, 14, 3716−3719. (i) Krompiec, S.; Kuznik, N.; Penczek, R.;
Rzepa, J.; Mrowiec-Bialøn, J. J. Mol. Catal. A - Chem. 2004, 219, 29−
40. (j) Scarso, A.; Colladon, M.; Sgarbossa, P.; Santo, C.; Michelin, R.
A.; Strukul, G. Organometallics 2010, 29, 1487−1497. (k) Hilt, G.
ChemCatChem 2014, 6, 2484−2485. (l) Mayer, M.; Welther, A.; Jacobi
von Wangelin, A. ChemCatChem 2011, 3, 1567−1571. (m) Jennerjahn,
R.; Jackstell, R.; Piras, I.; Franke, R.; Jiao, H.; Bauer, M.; Beller, M.
ChemSusChem 2012, 5, 734−739. (n) Clark, J. R.; Griffith, J. R.; Diver,
S. T. J. Am. Chem. Soc. 2013, 135, 3327−3330. (o) Gosser, L. W.;
Parshall, G. W. Tetrahedron Lett. 1971, 2555−2558.
(2) (a) Crabtree, R. H. The Organometallic Chemistry of the Transition
Metals, 3rd ed.; Wiley: New York, 2001; pp 226−228. (b) Larionov,
E.; Li, H.; Mazet, C. Chem. Commun. 2014, 50, 9816−9826.
(c) Knapp, S. M. M.; Shaner, S. E.; Kim, D.; Shopov, D. Y.;
Tendler, J. A.; Pudalov, D. M.; Chianese, A. R. Organometallics 2014,
33, 473−484.
(3) (a) Chen, C.; Dugan, T. R.; Brennessel, W. W.; Weix, D. J.;
Holland, P. L. J. Am. Chem. Soc. 2014, 136, 945−955. (b) Timsina, Y.
N.; Biswas, S.; RajanBabu, T. V. J. Am. Chem. Soc. 2014, 136, 6215−
́
6218. (c) Crossley, S. W. M.; Barabe, F.; Shenvi, R. A. J. Am. Chem.
Soc. 2014, 136, 16788−16791.
(4) (a) Schmidt, A.; Nodling, A. R.; Hilt, G. Angew. Chem., Int. Ed.
̈
2015, 54, 801−804. (b) Schmidt, A.; Hilt, G. Chem.Asian J. 2014, 9,
2407−2410.
(5) For recent applications of nickel catalysts in isomerization
reactions, see: (a) Lee, W.-C.; Wang, C.-H.; Lin, Y.-H.; Shih, W.-C.;
Ong, T.-G. Org. Lett. 2013, 15, 5358−5361. (b) Wang, L.; Liu, C.; Bai,
R.; Pana, Y.; Lei, A. Chem. Commun. 2013, 49, 7923−7925. (c) Wille,
A.; Tomm, S.; Frauenrath, H. Synthesis 1998, 305−308.
(6) dppp = 1,3-bis(diphenylphosphino)propane, dppe = 1,2-
bis(diphenylphosphino)ethane.
́ ́
(7) For selected reviews, see: (a) Yus, M.; Gonzalez-Gomez, J. C.;
Foubelo, F. Chem. Rev. 2013, 113, 5595−5698. (b) Ramadhar, T. R.;
Batey, R. A. Synthesis 2011, 1321−1346. (c) Pietruszka, J.; Schone, N.;
̈
Frey, W.; Grundl, L. Chem.Eur. J. 2008, 14, 5178−5197.
(d) Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763−2794. See
̌
also: (e) Susnik, P.; Hilt, G. Organometallics 2014, 33, 5907−5910.
(f) Hoffmann, R. W.; Gilles, N.; Schlapbach, A. Pure Appl. Chem. 1990,
D
DOI: 10.1021/acs.orglett.5b01230
Org. Lett. XXXX, XXX, XXX−XXX